Doxycycline inhibits vascular leakage and prevents ovarian hyperstimulation syndrome in a murine model.
OBJECTIVE
To determine whether doxycycline would inhibit the development of ovarian hyperstimulation syndrome (OHSS) in a murine model.


METHODS
Testing the effect of oral doxycycline treatment on gonadotropin-induced peritoneal capillary leakage in mice.


METHODS
Animal research facility.


METHODS
Four-week-old female C57Bl/6 mice.


METHODS
Ovarian hyperstimulation syndrome was induced in mice by administering gonadotropins for 3 days followed by human chorionic gonadotropin. Peritoneal vascular leakage was quantified using the Miles vascular permeability assay. Mice were treated with daily oral doxycycline or vehicle.


METHODS
The concentration of dye in abdominal fluid extracted by peritoneal lavage was measured spectrophotometrically. Ascites volume was determined using dye dilution.


RESULTS
Doxycycline inhibited peritoneal vascular leakage and ascites accumulation in the hormonally stimulated mice. Doxycycline treatment did not inhibit ovarian stimulation or ovulation when compared with controls, as indicated by similar ovarian morphology, ovarian weights, and corpora lutea counts. Importantly, vessel density within the corpora lutea was similar in the two groups.


CONCLUSIONS
Doxycycline prevents OHSS in a murine model without compromising ovarian stimulation. This effect is caused by inhibition of vascular leakage. Doxycycline's potential in preventing human OHSS is promising and warrants further studies.
Fainaru
Ofer
O
Department of Surgery, Vascular Biology Program, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. Ofer.Fainaru@childrens.harvard.edu
Hornstein
Mark D
MD
Folkman
Judah
J
D000818:Animals; D001201:Ascites / Q000517:prevention & control; D002199:Capillary Permeability / Q000187:drug effects*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004318:Doxycycline / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000517:prevention & control; D005260:Female; D006062:Gonadotropins / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D016471:Ovarian Hyperstimulation Syndrome / Q000473:pathology / Q000517:prevention & control*; D010053:Ovary / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D010062:Ovulation Induction / Q000379:methods
D004338:Drug Combinations; D006062:Gonadotropins; D004318:Doxycycline